BACKGROUND: The cardioselective β-1 receptor antagonist metoprolol is used to treat heart failure. It is metabolized in the liver, primarily by cytochrome 2D6. RESEARCH DESIGN AND METHODS: In this study, trough serum concentrations of metoprolol and its metabolite α-hydroxymetoprolol were measured in patients with heart failure with reduced ejection fraction. RESULTS: Concentrations were 1.3-122.9 µg/L for metoprolol and 1.3-125.7 µg/L for α-hydroxymetoprolol, metabolic ratios were 0.11-98.32. The median weight-adjusted apparent clearance of metoprolol was 53.07 (range 3.24-500.0). Metoprolol and α-hydroxymetoprolol concentrations correlated with both daily dose and dose per kilogram of body weight. However, metoprolol concentrations at the same daily dose showed a wide variability. Patients taking 100 mg/day had significantly lower NT-proBNP values than those taking 25 or 50 mg/day. Patients with LVEF ≤ 35% versus > 35% used significantly lower daily doses and doses per kilogram of body weight, although metoprolol concentrations did not differ. A poor cytochrome 2D6 metabolizer phenotype was detected in two patients. CONCLUSIONS: Metoprolol concentrations showed a wide interindividual variability at the same daily dose. Simultaneous determination of metoprolol and α-hydroxymetoprolol concentrations could identify patients at risk of possible accumulation of metoprolol leading to intoxication or, conversely, patients at risk of underdosing. [Figure: see text].

Department of Clinical Pharmacology Faculty of Medicine University of Ostrava Ostrava Czech Republic

Department of Clinical Pharmacology Institute of Laboratory Medicine University Hospital Ostrava Ostrava Czech Republic

Department of Internal Medicine and Cardiology University Hospital Ostrava Ostrava Czech Republic

Department of Internal Medicine Faculty of Medicine University of Ostrava Ostrava Czech Republic

References provided by Crossref.org